Karen Belkic, MD, PhD
- Karolinska Institute
Optimized Magnetic Resonance Spectroscopy for Early Ovarian Cancer Detection
When diagnosed early, ovarian cancer has an excellent prognosis, but current imaging methods for detecting ovarian cancer have not yet yielded the hoped-for benefit. Standard clinical magnetic resonance scanners produce images of poor quality, with low resolution and limited information content. However, magnetic resonance spectroscopy (MRS) could potentially reveal metabolic features of ovarian cancer that would reliably distinguish ovarian cancer from benign ovarian lesions. Dr. Belkic will be optimizing MRS for ovarian cancer detection using her advanced signal processing method, the fast Padé transform (FPT), which has already been shown to dramatically improve resolution and generate high-quality MRS data to detect ovarian cancer.
Ilana Chefetz-Menaker, PhD
- University of Michigan
Deciphering molecular mechanism of ALDH-inhibition driven necroptosis
Dr. Chefetz-Menaker recently demonstrated that chemotherapy resistant ovarian cancer stem-like cells (CSC) can be identified by a protein activity known as ALDH. The expression of ALDH in CSC allows a unique opportunity to develop therapeutics specifically targeting CSC, which are thought to be the cells involved in recurrence. Dr. Cheftez-Menaker has developed novel ALDH inhibitors which appear to induce ovarian CSC cell death via a necroptotic mechanism, which will be explored in this study to expand the understanding of ALDH inhibition-induced necroptosis and provide critical pre-clinical studies for a potential novel CSC targeted therapeutic to prevent recurrent disease.
Simon Chu, PhD
- Hudson Institute of Medical Research
PPARgamma Activation Augments Anticancer Effects of XIAP Inhibition in Ovarian Granulosa Cell Tumors
Granulosa cell tumors of the ovary arise due to dysfunction of the granulosa cells, which are support cells in the ovary, involved in ovulation and production of hormones. Dr. Chu will determine if using therapeutic drugs that act on critical cell signaling pathways, involving key genes for cell survival, will render these tumors more sensitive to chemotherapy. By identifying and manipulating unusual and distinctive patterns of key cell survival genes, he can develop tools for better prognostic indicators and potential new targets for granulosa cell tumor treatments.
Andrea Facciabene, PhD
- University of Pennsylvania
Tumor development influences gut flora – possible implication in early detection
Early detection of ovarian cancer represents the best hope for mortality reduction and long-term disease control. Dr. Facciabene’s preliminary data indicate that developing ovarian cancer induces change in the microorganisms found in the gut, also known as the gut microbiome. Previously, controlled studies have demonstrated the existence of skin and saliva microbiome signatures in breast and pancreatic cancer, respectively. Dr. Facciabene hypothesizes that using a combination of next-generation sequencing (NGS) and metagenomics analysis, a sensitive and specific screening test for ovarian cancer can be developed through the analysis of the gut microbiome.
Paul Goodfellow, MS, PhD
- Ohio State University
Role of BRIP1 helicase missense mutations in ovarian cancer
BRIP1 gene has recently been recognized as an ovarian cancer susceptibility gene, based primarily on discovery of mutations that result in a truncated, or shortened, BRIP1 protein that no longer functions properly. Most genetic variation in the BRIP1 gene, however, does not lead to a shortened form of the protein, but some variants may still lead to protein dysfunction. Dr. Goodfellow will determine which BRIP1 gene variants have disrupted BRIP1 protein function and mostly likely could result in the development of ovarian cancer by developing mouse strains carrying defective Brip1 genes to study how certain mutant proteins lead to ovarian tumors. Together, these studies will allow for new approaches to prevent and treat ovarian cancer.
Weei-Chin Lin, MD, PhD
- Baylor College of Medicine
Target a new mechanism of checkpoint defect in ovarian cancer
Normal cellular growth is regulated by a process called replication checkpoint. Most ovarian cancers contain the tumor suppressor p53 that is mutated and therefore interferes with proper replication checkpoint function. Dr. Lin’s preliminary data uncovered a novel activity in mutant p53 that is responsible for replication checkpoint defects. By performing a large-scale compound screen, he has identified novel compounds that target the checkpoint defect. Dr. Lin will now test the antitumor activity of two active compounds in ovarian cancer to see if p53 can be targeted to restore replication checkpoint functions that would inhibit cancer growth.
Iain McNeish, MD, PhD, FRCP
- University of Glasgow
Improved models of high grade serous ovarian cancer
To understand how cancers grow and spread within patients, it is essential that researchers have realistic and simple animal models that accurately recreate the mutations seen in the DNA of human cancers. Dr. McNeish will use a new technique, called CRISPR/Cas9 gene editing, to alter the DNA in a mouse model of ovarian cancer, specifically creating mutations seen in human high grade serous ovarian cancer. This new mouse model will used to identify key abnormalities in the DNA of tumor cells that drive changes in the environment surrounding the tumor, especially the interactions with the immune system.
Natasa Obermajer, PhD
- University of Pittsburgh
Taming MDSC-controlled Th17-to-Treg cell conversion in ovarian cancer
Regulatory T (Treg) cells are part of the immune system and have been shown in ovarian cancer to suppresses immune cell activity and prevent the immune system from fighting ovarian cancer cells. Dr. Obermajer has shown that another type of immune system cell called T helper 17 (Th17) cells can be converted into Treg cells by the presence of myeloid-derived suppressor cells. She will identify the steps needed to convert Th17 cells into Treg cells and determine whether it is possible to do the reverse conversion of Treg cells into Th17 cells because Th17 cells have a strong anti-tumor activity that can be harnessed to fight ovarian cancer.
Erinn Rankin, PhD
- Stanford University
- 2016 Pape Family Pilot Study Award
Targeting the hypoxic secretome in omental metastasis
Mesothelial cells line the abdominal cavity and play an important role in ovarian cancer metastasis. These mesothelial cells in the presence of ovarian cancer tumors are deprived of oxygen (hypoxic) and, as a result, produce components of the hypoxia inducible factor (HIF) signaling pathway that allow them to “talk” to ovarian cancer tumor cells and promote metastasis. By targeting mesothelial cells in the treatment of ovarian cancer, Dr. Rankin hopes to interrupt the signals that promote metastasis and limit the spread of ovarian cancer cells throughout the patient’s body.
Jill Slack-Davis, PhD
- University of Virginia
Detailed characterization of tumor initiation in a novel mouse model of high-grade serous ovarian cancer
Early detection remains the best approach for successful treatment of cancer, including ovarian cancer, as patients with early stage cancer have the best chance of survival. There is an urgent need to identify specific biomarkers for early detection and to understand the earliest time points in cancer progression to guide effective clinical intervention. Dr. Slack-Davis is developing a novel mouse model for ovarian cancer that can immediately and permanently track individual cells, at the time of the earliest genetic mutations that eventually lead to ovarian cancer. By knowing the earliest genetic mutations, early detection biomarkers can be developed to indicate the presence of ovarian cancer.
Varatharasa Thiviyanathan, PhD
- University of Texas Health Science Center at Houston
Multi-functional RNA Nanoparticles for targeted Delivery of Therapeutics for Ovarian Cancer
Since majority of the ovarian cancer cases are detected at later stages, novel therapeutic approaches are critically needed to improve the overall survival rates. Targeted delivery of therapeutics where drugs can be delivered specifically to the cancer cells without causing damage to normal cells is a promising approach to treat ovarian cancer. Dr. Thiviyanathan will develop a new class of affinity molecules that can recognize the cancer cells. He will use multifunctional nanoparticles made up of RNA to attach the affinity molecules to act as homing devices to deliver the therapeutic drugs to the cancer cells.
Andrew Wilson, PhD
- Vanderbilt University
Prognostic Significance of TR3/NR4A1 Expression in Ovarian Cancer
A key clinical problem in the management of advanced ovarian cancer is tumor resistance to traditional platinum drugs and to newer drugs that inhibit the PARP protein (PARPi). Dr. Wilson will investigate an innovative approach to improve the effects of platinum drugs and PARPi. He has shown that the TR3 protein, which kills ovarian cancer cells, is reduced in tumors resistant to these platinum and PARPi drugs. By activating TR3 function in ovarian cancer cells that are being treated with platinum drugs and PARPi, he hopes to improve drug response and benefit a large number of women with advanced disease.